p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer.
OBJECTIVE
Thirty percent of women with node-negative breast cancer will have a recurrence within 10 years after diagnosis. Molecular markers may identify those patients and predict whether they benefit from adjuvant therapy. The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare perioperative treatment with one course of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus no further therapy. We studied tumors from premenopausal patients with node-negative breast cancer randomized in this trial to determine whether p53 accumulation, c-erbB-2 expression, percentage of Ki-67-positive cells, estrogen receptor (ER-immunoassay [IA]), progesterone receptor (PR-IA), and angiogenesis could be used as prognostic factors and predictors of responsiveness to adjuvant chemotherapy.


METHODS
Paraffin-embedded tumor specimens from 441 premenopausal women with node-negative breast cancer were collected from the larger EORTC trial. Paraffin sections from the tumors were analyzed for immunohistochemical expression of p53, c-erbB-2, Ki-67, ER, PR, and angiogenesis.


RESULTS
Patients with p53-negative tumors showed a significant benefit from perioperative chemotherapy (P < .01), whereas patients who had p53-positive tumors did not (P = .80). At a median follow-up time of 49 months, univariate analyses for disease-free survival (DFS) failed to show prognostic value for p53, c-erbB-2 and angiogenesis. Both univariate and multivariate results showed Ki-67 positivity, ER-IA negativity, and a younger age to be associated with a worse prognosis.


CONCLUSIONS
p53 accumulation was associated with a poor response to one perioperative course of FAC chemotherapy. Ki-67, ER-IA, and age are important prognostic factors in premenopausal women with node-negative breast cancer.
Clahsen
P C
PC
European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.
van de Velde
C J
CJ
Duval
C
C
Pallud
C
C
Mandard
A M
AM
Delobelle-Deroide
A
A
van den Broek
L
L
Sahmoud
T M
TM
van de Vijver
M J
MJ
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D017697:Premenopause; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53